Polesskaya Anna, Seale Patrick, Rudnicki Michael A
Ottawa Health Research Institute, Molecular Medicine Program, 501 Smyth Road, Ottawa, Ontario, Canada K1H 8L6.
Cell. 2003 Jun 27;113(7):841-52. doi: 10.1016/s0092-8674(03)00437-9.
The observation that CD45(+) stem cells injected into the circulation participate in muscle regeneration raised the question of whether CD45(+) stem cells resident in muscle play a physiological role during regeneration. We found that CD45(+) cells cultured from uninjured muscle were uniformly nonmyogenic. However, CD45(+) cells purified from regenerating muscle readily gave rise to determined myoblasts. The number of CD45(+) cells in muscle rapidly expanded following injury, and a high proportion entered the cell cycle. Investigation of candidate pathways involved in embryonic myogenesis revealed that Wnt signaling was sufficient to induce the myogenic specification of muscle-derived CD45(+) stem cells. Moreover, injection of the Wnt antagonists sFRP2/3 into regenerating muscle markedly reduced CD45(+) stem cell proliferation and myogenic specification. Our data therefore suggest that mobilization of resident CD45(+) stem cells is an important factor in regeneration after injury and highlight the Wnt pathway as a potential therapeutic target for degenerative neuromuscular disease.
循环系统中注入的CD45(+)干细胞参与肌肉再生这一观察结果，引发了肌肉中驻留的CD45(+)干细胞在再生过程中是否发挥生理作用的问题。我们发现，从未受伤肌肉中培养的CD45(+)细胞均不具有成肌能力。然而，从再生肌肉中纯化出的CD45(+)细胞很容易产生定向成肌细胞。损伤后，肌肉中CD45(+)细胞数量迅速增加，且很大一部分进入细胞周期。对参与胚胎肌生成的候选信号通路的研究表明，Wnt信号足以诱导肌肉来源的CD45(+)干细胞发生成肌分化。此外，向再生肌肉中注射Wnt拮抗剂sFRP2/3可显著降低CD45(+)干细胞的增殖和成肌分化。因此，我们的数据表明，驻留的CD45(+)干细胞的动员是损伤后再生的一个重要因素，并突出了Wnt信号通路作为退行性神经肌肉疾病潜在治疗靶点的重要性。
